The current view of the mechanism by which thymus-derived (T) lymphocytes affect the response of thymus-independent (B) lymphocytes to antigen is that T lymphocytes control the initial recognition of antigen by specific B lymphocytes. Thus, the failure of thymus-deprived mice to produce antibody upon immunization with a thymus-dependent antigen is thought to be due to a lack of stimulation of specific B cells. In preliminary experiments on the response to dinitrophenyl hemocyanin (DNP-KLH) of adult AKR mice which had been thymectomized, irradiated and reconstituted with bone marrow cells (Tx-BM), results which are inconsistent with this view were obtained. We found that DNP-specific B cells, which are detected by an antigen-binding assay, proliferated normally after immunization, but that the final stages of differentiation of these cells were not reached. Thus, Tx-BM animals produced IgM, but not IgG antibody. At least three stages of B cell differentiation can be discerned at present in the mouse. The proposed research is concerned with in vivo and in vitro analysis of the effects of T cells or their products on the differentiation of DNP-specific B cells. Analysis will involve the immune response of Tx-BM and thymus-aplastic ("nude") mice. In addition, Mishell-Dutton cultures and the tandem cultures of Feldmann will be used to investigate the mechanism(s) by which T cell effects are mediated. Clarification of the events of terminal differentiation of B cells and the influence of T cells on this differentiation will lead to better understanding of immune responses.